In the last 5-10 years there has been numerous data to suggest the presence of endothelial progenitor cells (EPCs) that can be recruited from the bone marrow in adult animals and in humans (Rafii and Lyden, Nat Med, 2003. 9(6):702-12). Several papers have strongly suggested the therapeutic potential of these cells. For example, Murohara, et al., and Kalka et al., have reported that infusion of selected populations of cells from the bone marrow in animals improves angiogenesis in ischemic limbs (Murohara et al., J Clin Invest, 2000. 105(11):1527-36; Kalka et al., PNAS, 2000. 97(7):3422-3427). Furthermore, Dacron grafts implanted in dogs were reportedly endothelialized exclusively by cells from transplanted bone marrow (Shi et al., Blood, 1998. 92(2):362-7). Two studies reported in humans have also been significant. Left ventricular assist devices (LVADs) removed after 6 months were reported to be colonized by CD34+ and VEGFR2+ endothelial and hematopoietic cells, both markers for early progenitor cells (Rafii et al., Ann Thorac Surg, 1995. 60(6):1627-32). In addition, autologous transplantation of bone marrow cells reportedly improved patient peripheral vascular disease (Tateishi-Yuyama et al., Lancet, 2002. 360(9331):427-35). Thus, this cell population exists in the bone marrow and can improve significant pathophysiological cardiovascular conditions, according to these studies.
These and other animal studies have experimented with the vasculogenic potential of bone marrow by either delivering whole bone marrow transplants or selected cell populations via intravenous or intramuscular administration (Tateishi-Yuyama et al., Lancet, 2002. 360(9331):427-35; Edelberg et al., Circ Res, 2002. 90(10):E89-93; Heissig et al., Cell, 2002. 109(5):625-37; Young et al., Proc Natl Acad Sci, 2002. 99(18):11951-6; Murayama et al., Exp. Hematol, 2002. 30(8):967-72). These bone marrow derived EPCs appear to be attracted to angiogenic foci in the peripheral vasculature (Edelberg et al., Circ Res, 2002. 90(10):E89-93; Lyden et al., Nature and Medicine, 2001. 7:1194-1201). Recent work has reported the ability to mobilize and recruit these cells using adenoviral vectors expressing angiogenic factors and recombinant proteins like VEGF, angiopoietin 1 and stromal derived factor-1 into the bloodstream (Rafii et al., Gene Therapy, 2002. 9:631-641; Hattori et al., J. Exp. Med., 2001. 193(9):1005-1014). Others have also examined the factors that govern the recruitment of endothelial progenitor cells (Kalka et al., PNAS, 2000. 97(7):3422-3427; Asahara et al., Science, 1997. 275(5302):964-7; Asahara et al., EMBO, 1999. 18(14):3964-3972).